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Sleep Disorders Project

Research on sleep disorders; understand the etiology and pathophysiology

Project Leader Makoto Honda

Project Leader
Makoto Honda

Research Summary

Our goal is to find the causes and develop better treatments for Narcolepsy and Hypersomnia.

Narcolepsy is a sleep disorder of abnormal intrinsic sleep-wake regulation, resulting in unique symptoms including frequent lapses into sleep, nocturnal sleep instability, and REM sleep related manifestations such as cataplexy (abrupt loss of muscle tone triggered by emotion), sleep paralysis, and hypnagogic hallucination.

Narcolepsy is associated with a deficiency of wake-promoting orexin/hypocretin producing neurons localized in the hypothalamus, and virtually all the patients carry human leukocyte antigen (HLA)-DQB1*06:02.

We are trying to solve the mystery of narcolepsy

Narcolepsy is associated with a variety of physical and psychiatric comorbid conditions. Since appropriate wakefulness is essential for higher brain functions, abnormal sleep-wake regulation can lead to various associated features. Despite the progress in sleep research fields, we currently have inadequate symptom-based treatments for sleep disorders, including narcolepsy. We are trying to elucidate the pathophysiology of narcolepsy with multifaceted problems to improve the QOL of hypersomnia patients.

Selected Publications

  • Honda M et al(2021) “Evaluation of pathological sleepiness by Multiple Sleep Latency Test and 24-hour polysomnography in patients suspected of idiopathic hypersomnia.” Psychiatry Clin Neurosci 75:149-151
  • Natsubori A,et al (2020) “In vivo state-dependent dynamics of cellular energy status in cortical neurons”. Communications Biol 3 491
  • Shimada M et al (2020) Metabolome analysis using cerebrospinal fluid from narcolepsy type 1 patients. Sleep zsaa095.
  • Shimada M et al. (2020) “Epigenome-wide association study of narcolepsy-affected lateral hypothalamic brain and overlapping DNA methylation profiles between narcolepsy and multiple sclerosis”. Sleep 43(1):zsz198
  • Miyagawa T et al (2019) “A missense variant in PER2 is associated with delayed sleep-wake phase disorder in a Japanese population”. J Hum Genetics, 64(12):1219-1225
  • Shimada M, et al. (2018) “Epigenome-wide association study of DNA methylation in narcolepsy: an integrated genetic and epigenetic approach.” Sleep 41:zsy019
  • Toyoda H, et al. (2017) “Narcolepsy susceptibility gene CCR3 modulates sleep-wake patterns in mice.” PLoS ONE 12:e0187888
  • Miyagawa T, et al. (2013) “Effects of oral L- carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.” PLoS ONE 8:e53707.
  • Miyagawa T, et al. (2011) “Abnormally low serum acylcarnitine levels in narcolepsy patients.” Sleep 34:349-353.